Meiosis and sporulation in the eukaryotic yeast Saccharomyces cerevisiae can be initiated by the partial deprivation of purine nucleotide and most effectively by the deprivation of guanine nucleotides (GTP). This differentiation can also be caused by partial deprivation of sulfur or methionine which in turn results in the decrease of intracellular concentrations of S-adenosylmethionine (SAM), methionyl-tRNAMET, and GTP. Experiments are underway to determine which of these compounds control sporulation. We have also begun to determine some structural and genetic changes which are involved in meiosis. A method has been developed to isolate large numbers of nuclei and nuclear matrices rapidly and cleanly. Two-dimensional electrophoresis was used to determine qualitative and quantitative changes in nuclear proteins and in DNA associated with the nuclear matrix.